Basis to Aid Crisis: Favipiravir Oral Solution for Hospital Compounding During COVID-19 Drug Shortage.

The COVID-19 pandemic outbreak has been overwhelming the healthcare system worldwide. A rapidly growing number of younger pediatric patients in Thailand necessitated the formulation of favipiravir, the most locally accessible antiviral agent against COVID-19, into a child-friendly dosage form as a safer alternative to a dispersion of crushed tablets in simple syrup. While striving to quickly develop a liquid formulation that is feasible for any local hospital production units, an oral solution was chosen due to its simplicity. Despite the large dose and poor aqueous solubility of favipiravir, a combination of pH control and use of poloxamer as a solubilizing agent has enabled us to streamline the manufacturing process of a 200 mg/15 mL oral solution for hospital compounding. To ensure its efficacy and safety, a specification for quality control was also established in accordance with the ICH quality guidelines and USP. The finished product stability was subsequently demonstrated under the conditions of 5°C ± 3°C, 25°C ± 2°C/75% RH ± 5% RH, 30°C ± 2°C/75% RH ± 5% RH, and 40°C ± 2°C/75% RH ± 5% RH. The results indicated that our formulation can be stored at 30°C ± 2°C/75% RH for 30 days, which will very well serve the need to allow drug distribution and patient use during the crisis, while the shelf-life can be extended to 60 days when stored at 5°C ± 3°C. Thus, accessibility to an essential medical treatment has been successfully enhanced for pediatric patients in Thailand and neighboring countries during the COVID-19 outbreak.

Pharmacokinetic Comparison of Favipiravir Oral Solution and Tablet Formulations in Healthy Thai Volunteers.

This study compared the pharmacokinetics and safety of favipiravir oral solution with those of tablet formulations, which were agents repurposed to treat nonsevere coronavirus disease 2019 in Thailand. In an open-label, single-dose, randomized, crossover study, 24 healthy subjects under fasting conditions were randomly assigned to a single dose of 200 mg of favipiravir, either as an oral solution of 200 mg/15 mL (test product) or a tablet (reference product), separated by a 7-day washout period. Fifteen plasma samples were collected over 12 hours after drug administration. Plasma favipiravir levels were quantified using in-house developed ultra-high-performance liquid chromatography-tandem mass spectrometry. The test/reference geometric mean ratio along with 90%CI for the maximum plasma concentration, area under the concentration-time curve (AUC) to the time of the last quantifiable concentration, and AUC after single-dose administration, extrapolated to infinity were 115.3% (90%CI, 107.7%-123.3%), 100.4% (90%CI, 96.9%-104.0%), and 100.4% (90%CI, 96.8%-104.2%), respectively. These results were within the predefined acceptance criteria for bioequivalence (80.0%-125.0%). No adverse events were observed in either group. The oral solution formulation could offer the advantage of easier swallowing in broader patient groups.